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Double wave vector diffusion weighting uses gradients along two different directions between excitation and acquisition. It has been shown theoretically that for restricted diffusion the signal amplitude in such an experiment can depend on the angle between the two gradient vectors. The highest amplitude is obtained with antiparallel orientation, and the amplitude difference between parallel and antiparallel gradient orientations depends on the compartment size. The validity of this description is experimentally tested for water between polymer beads, for radish, and for porcine spinal cord, using a clinical MR system with limited gradient strength. The results indicate that the phenomenon is observable; however, the size of the signal difference is considerably diminished when compared with theory. This is attributed to violations of the approximating conditions underlying the theoretical description and to free diffusion contributions. It is concluded that the effect could successfully be used as a basis for developing a new noninvasive method for assessing cell size. Magn Reson Med, 2008. © 2008 Wiley-Liss, Inc.